Over the last decades, breast-conserving surgery followed by whole breast irradiation became the standard of care for the treatment of early-stage breast carcinoma. However, the necessity of giving whole breast irradiation for all patients after breast conserving surgery has been questioned, due to serious side effects caused by the external beam radiation. In recent years, many studies compared whole breast irradiation with partial breast irradiation, whether in the form of intraoperative single dose radiation or brachytherapy (the treatment of cancer at a short distance with a radioactive isotope placed on, in, or near the lesions or tumor) applied to the surgical site following surgery. Both methods were found to have the same effectiveness while brachytherapy had less toxic side effects. Conventional brachytherapy for breast conservation requires the insertion of 14 to 20 catheters per procedure and needs complex techniques such as CT guided surgery to place the catheters in the vicinity of the tumor bed. An alternative approach is the MammoSite RTS device, where a single catheter is used to inflate a balloon loaded with the radioisotope in the post lumpectomy cavity immediately or up to 10 weeks post lumpectomy.
Despite clear advantages of brachytherapy over conservative radiotherapy in the treatment of cervical cancer and selected soft tissue sarcomas of the extremities, some major constraints are associated with its implementation in breast cancer and other soft tissue sarcomas. These include the need for general anesthesia or intravenous sedation, complicated placement procedures (especially in the case of interstitial brachytherapy by catheters) and the need for post treatment reexcision for device removal in both methods of catheters and MammoSite, and/or to treat infections associated with the device. Therefore, an alternative mode of local radiotherapy is warranted.
Similarly, cancers of the brain and the central nervous system affect approximately 135,000 people in the USA who are living with a diagnosis of a malignant brain tumor. The current standard of care includes maximal safe surgical resection, followed by a combination of radiation and chemotherapy; resulting in median survival of 14.6 months and the percentage of patients alive at 2 years is approximately 26%.
Due to the short mean survival, frequent recurrences, and poor prognosis associated with the tumors, new therapeutic strategies were investigated consecutively including local drug delivery approaches. Interstitial radiotherapy (brachytherapy) has been suggested using 125I and 192Ir temporary and permanent implants. Interstitial high-dose-rate therapy needed complicated implantation techniques such as CT-guided surgery, and was frequently associated with relatively high toxicity. Interstitial low-dose-rate therapy, temporary implants are preferred as permanent implants bear an increased risk of prolonged edema. Brachytherapy with temporary implants may lead to prolonged survival in patients with recurrent glioma, but it is associated with morbidity and relatively high costs. It is associated with fewer side effects compared to high-dose-rate approaches, although randomized approaches are lacking. A third approach is the GliaSite, a technological alternative to seed-implantation, in which radiation is applied via a surgically inserted balloon catheter which is filled with a liquid 125I containing solution to deliver a high-dose-rate therapy. This device is showing promising results in the recurrent disease setting; however, this approach has some shortcomings in terms of uncertainties of dose distribution, side effects and the invasiveness in a highly palliative treatment setting.
Despite the clear advantage of the brachytherapy with solid hydrogel implants, previous solid implants did not fill the surgical cavity which raised questions about the homogeneity of the radiation in the surgical margins. Another limitation of the solid hydrogels was the leakage of the radioactivity to adjacent normal tissues which was observed in the first week after implantation. Therefore, an efficient way to prevent leakage of radioactivity from the implant during the treatment is warranted. Due to the short mean survival, frequent recurrences, and poor prognosis, particularly with breast cancer and glioma, new therapeutic strategies are warranted.